rs34138162

Variant names:

• chr10-129466959-C-A
• rs34138162
• ENST00000306010.8:c.-257C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-129466959-C-A
• chr10-129466959-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000306010.8(MGMT):​c.-257C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 152,100 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.039 (195 hom., cov: 33)
• Consequence: MGMT ENST00000306010.8 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

Genes affected

MGMT (HGNC:7059): (O-6-methylguanine-DNA methyltransferase) Alkylating agents are potent carcinogens that can result in cell death, mutation and cancer. The protein encoded by this gene is a DNA repair protein that is involved in cellular defense against mutagenesis and toxicity from alkylating agents. The protein catalyzes transfer of methyl groups from O(6)-alkylguanine and other methylated moieties of the DNA to its own molecule, which repairs the toxic lesions. Methylation of the genes promoter has been associated with several cancer types, including colorectal cancer, lung cancer, lymphoma and glioblastoma. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0395 (6002/152100) while in subpopulation AMR AF= 0.0515 (787/15296). AF 95% confidence interval is 0.0485. There are 195 homozygotes in gnomad4. There are 3176 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 195 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGMT	ENST00000306010.8	c.-257C>A		upstream_gene_variant		1		ENSP00000302111.7

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6005 AN: 151990 Hom.: 195 Cov.: 33

Gnomad AFR AF: 0.00770

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0136

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0395 AC: 6002 AN: 152100 Hom.: 195 Cov.: 33 AF XY: 0.0427 AC XY: 3176 AN XY: 74376

Gnomad4 AFR AF: 0.00768

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0953

Gnomad4 EAS AF: 0.0132

Gnomad4 SAS AF: 0.0274

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0447

Gnomad4 OTH AF: 0.0403

Alfa AF: 0.0490 Hom.: 40

Bravo AF: 0.0347

Asia WGS AF: 0.0290 AC: 99 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34138162; hg19: chr10-131265223;